加味孔圣枕中丹对慢性脑缺血痴呆大鼠VEGF表达和微血管密度的影响

Impacts of modified Kongshengzhenzhong Pills on expression of VEGF and MVD in VD rats induced by chronic cerebral ischemia

目的观察加味孔圣枕中丹对慢性脑缺血致血管性痴呆(VD)大鼠学习记忆能力及脑血管内皮生长因子(VEGF)表达和微血管密度(MVD)的影响,探讨该方影响血管生成、改善学习记忆能力的可能机制。方法将SD大鼠随机分为假手术组、模型组、加味孔圣枕中丹组和贝伐单抗组,除假手术组外,其余组均采用双侧颈总动脉永久结扎法建立慢性脑缺血痴呆大鼠模型。造模24 h后,加味孔圣枕中丹组及贝伐单抗组均给予加味孔圣枕中丹水煎浓缩液16 m L/(kg·d)灌胃,模型组和假手术组给予等容量生理盐水灌胃,均1次/d,连续30 d。贝伐单抗组另给予贝伐珠单抗注射液2 mg/kg腹腔注射,1次/2周。干预结束后,Morris水迷宫检测各组大鼠逃避潜伏期评价学习记忆能力,免疫组化法检测皮质及胼胝体VEGF和CD34表达情况,以CD34标记MVD。结果与假手术组比较,模型组大鼠逃避潜伏期明显延长(P<0.05),胼胝体VEGF表达水平升高(P<0.05),皮质和胼胝体MVD显著升高(P均<0.05);与模型组比较,加味孔圣枕中丹组大鼠逃避潜伏期缩短(P<0.05),皮质及胼胝体VEGF表达水平、MVD均显著升高(P均<0.05);与贝伐单抗组比较,加味孔圣枕中丹组皮质VEGF表达水平及MVD均显著升高(P均<0.05)。结论加味孔圣枕中丹能上调慢性脑缺血大鼠脑组织VEGF表达,促进脑组织血管生成,这可能是其改善痴呆模型大鼠学习记忆能力的作用机制之一。

Objective It is to observe the impacts of modified Kongshengzhenzhong Pills on the ability of learning and memory,as well as the expression of VEGF protein and the micro vessel density （MVD）in brain tissue of the vascular dementia （ VD） rats induced by chronic cerebral ischemia ,and to explore the effects of this decoction on angiogenesis and its mechanism of improving learning and memorizing ability .Methods Rat models of VD induced by chronic cerebral ischemia was prepared by bilateral common carotid artery ligation .The experimental animals were randomly divided into sham operation group , model group, modified Kongshengzhenzhong Pills group , and Bevacizumab group .Drug intervention was carried out for 30days.The ability of learning and memorizing of the rats was assessed by Morris water maze experiment .The expression of VEGF protein and CD34 both in cortex and callosum were detected by immunohistochemistry , and MVD was calculated .Results Compared with the sham operation group , the average escape latent period prolonged , the expression of VEGF in callosum , MVD both in cortex and callosum increased in the model group （P〈0.05）.Compared with the model group , the average escape latent pe-riod shortened , the expression of VEGF and MVD both in cortex and callosum increased significantly in modified Kongsheng -zhenzhong Pills group（P〈0.05）.Conclusion Modified Kongshengzhenzhong Pills can elevate the expression of VEGF protein and promote blood vessel formation in brain tissue of VD rats .And these effects may serve as one of its mechanisms of impro-ving learning and memorizing ability of VD rats .